A body of evidence has been collected which points to the fact that at least some cultured human leukemic cells and cultured as well as freshly isolated rodent leukemic cells have an absolute nutritional requirement for pre-formed L-cystine. In essence, they behave phenotypically like cystine auxotrophs. The biochemical basis for this growth requirement appears to be, at least in part, an intracellular depletion of cystathionase (CSE), the enzyme which catalyzes the last step in the L-CYS biosynthetic pathway. Our goal is to determine the prevalence of the CYS minus/CSE minus phenotype among freshly isolated human tumor cells - from patients with both hematologic malignancy and solid tumor diseases. We will also attempt to learn whether, in certain instances, this phenotype is specific to tumor, as opposed to normal cells. Using a specific cystathionase radioimmunoassay, we will also ask whether CYS minus/CSE minus cells synthesize less CSE protein than CYS plus/CSE plus cells. If so, using a fluorescent labelled anti-CSE IgG, we will attempt to develop a sorting method which will discriminate between CSE plus and CSE minus cells. The goal of such an effort would be the ability to detect otherwise occult tumor cells in readily accessible cell reservoirs in the body. Another major hope is that we can derive enough information to serve as the basis for a specific therapeutic approach to certain human tumors using cystine degrading enzymes. BIBLIOGRAPHIC REFERENCE: Iglehart, J.D., York, R.M., Modest, A.P., Lazarus, H., and Livingston, D.M. Cystine Requirement of Continuous Human Lymphoid Cell Lines of Normal and Leukemic Origin. J. Biol. Chem. 1977, in press.